CRCNS Research Proposal: Contributions of the Thalamus and Basal Ganglia to Neocortical Beta Oscillation: A Novel Computational Hypothesis

80多年来，研究人员观察到新皮质中有节奏的电活动，新皮质是覆盖哺乳动物大脑的神经元的外壳。尽管这些振荡普遍存在，但它们对计算的意义--它们是否以及如何帮助我们移动、感知和/或思考--仍然是一个激烈辩论的话题。β振荡，即15&29赫兹的节律性活动，在新皮质中显著。β蛋白的过度表达是帕金森氏症的一个特征，缓解其运动症状的治疗也会减少β蛋白的表达。同样，β振荡预示着人类受试者感知感官刺激的失败。这些发现直接暗示了贝塔对于信息处理和健康大脑功能的重要性。了解贝塔的详细来源对于了解其作用和潜在地指导靶向治疗至关重要。本研究将检验最近发展起来的一项假说，该假说解释了贝塔在人脑中的自然表达模式。这一假说源于一个详细的生物物理学精确的多区域计算神经模型。为了验证这一假设，这项拟议的研究将使用对多个大脑区域的详细模拟来指导实验记录和大脑刺激。这些数据将反过来用于推进和约束模型。作为这项研究的一部分，该模型将详细说明包括来自基底节、丘脑和新皮质的相互联系的元素。这些相同的区域将成为神经记录的目标，以了解它们的活动如何与处理感觉信息的麻醉和行为准备中的新皮质β相关。模型预测的因果检验将通过利用光遗传学的最新创新来实现，光遗传学应用光脉冲以毫秒的精度和细胞类型的特异性打开和关闭神经元。光遗传学将在一个真实的大脑中测试该模型预测的导致这种大脑节奏表达的活动模式的充分性和必要性。

For over 80 years, researchers have observed rhythmic electrical activity in the neocortex, the outer shell of neurons covering the mammalian brain. Despite the prevalence of these oscillations, their meaning for computation--if and how they help us move, perceive and/or think--is a topic of intense debate. Beta oscillations, rhythmic activity at 15‐29 Hz, are prominent in neocortex. Overexpression of beta is a hallmark of Parkinson's disease, and treatments that relieve its motor symptoms also diminish beta. Similarly, beta oscillations predict failure by human subjects to perceive sensory stimuli. These findings directly implicate beta as important for information processing and healthy brain function. Understanding the detailed origins of beta is crucial to knowing its role and to potentially guiding targeted therapies.The present study will test a recently developed hypothesis that explains the natural expression patterns of beta in the human brain. This hypothesis emerged from a detailed biophysically accurate and multi‐area computational neural model. To test this hypothesis, the proposed research will use detailed simulations of multiple brain areas to guide experimental recordings and brain stimulation. These data will in turn be used to advance and constrain the model. As part of this research, the model will be elaborated to include interconnected elements from the basal ganglia, thalamus and neocortex.These same areas will be targets for neural recording, to understand how their activity correlates with neocortical beta in anesthetized and behaving preparations processing sensory information. Causal testing of model predictions will be achieved by leveraging recent innovations in optogenetics, the application of light pulses to turn neurons on and off with millisecond precision and cell-type specificity. Optogenetics will test in a real brain the sufficiency and necessity of the activity patterns that are predicted by the model to lead to expression of this brain rhythm.